title: PLS3 mutations in X-linked osteoporosis with fractures.
abstract: Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F-actin) bundles, appears to be important in human bone health, on the basis of pathogenic variants in PLS3 in five families with X-linked osteoporosis and osteoporotic fractures that we report here. The bone-regulatory properties of PLS3 were supported by in vivo analyses in zebrafish. Furthermore, in an additional five families (described in less detail) referred for diagnosis or ruling out of osteogenesis imperfecta type I, a rare variant (rs140121121) in PLS3 was found. This variant was also associated with a risk of fracture among elderly heterozygous women that was two times as high as that among noncarriers, which indicates that genetic variation in PLS3 is a novel etiologic factor involved in common, multi-factorial osteoporosis.
authors.affiliation: Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Fleur S
authors.initials: FS
authors.lastname: van Dijk
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Dimitra
authors.initials: D
authors.lastname: Micha
authors.forename: Markus
authors.initials: M
authors.lastname: Riessland
authors.forename: Carlo L M
authors.initials: CL
authors.lastname: Marcelis
authors.forename: Christine E
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: Janine
authors.initials: J
authors.lastname: Milbradt
authors.forename: Anton A
authors.initials: AA
authors.lastname: Franken
authors.forename: Arjan J
authors.initials: AJ
authors.lastname: Harsevoort
authors.forename: Klaske D
authors.initials: KD
authors.lastname: Lichtenbelt
authors.forename: Hans E
authors.initials: HE
authors.lastname: Pruijs
authors.forename: M Estela
authors.initials: ME
authors.lastname: Rubio-Gozalbo
authors.forename: Rolf
authors.initials: R
authors.lastname: Zwertbroek
authors.forename: Youssef
authors.initials: Y
authors.lastname: Moutaouakil
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Egthuijsen
authors.forename: Matthias
authors.initials: M
authors.lastname: Hammerschmidt
authors.forename: Renate
authors.initials: R
authors.lastname: Bijman
authors.forename: Cor M
authors.initials: CM
authors.lastname: Semeins
authors.forename: Astrid D
authors.initials: AD
authors.lastname: Bakker
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
authors.forename: Jenneke
authors.initials: J
authors.lastname: Klein-Nulend
authors.forename: Natalia
authors.initials: N
authors.lastname: Campos-Obando
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: Annemieke J M H
authors.initials: AJ
authors.lastname: Verkerk
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maugeri
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Quinten
authors.initials: Q
authors.lastname: Waisfisz
authors.forename: Hanne
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: Brunhilde
authors.initials: B
authors.lastname: Wirth
authors.forename: Marleen E H
authors.initials: ME
authors.lastname: Simon
authors.forename: Gerard
authors.initials: G
authors.lastname: Pals
mesh_terms: D000328:Adult; D000818:Animals; D015519:Bone Density / Q000235:genetics; D016723:Bone Remodeling / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D010024:Osteoporosis / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055815:Young Adult; D015027:Zebrafish
chemical_list: D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C026742:plastin